Phenotoin produces effects on palatal differentiation in humans and experimental animals which are quite similar to those produced by glucocorticoids. This grant proposes to examine the hypothesis that phenytoin may have a similar biochemical mechanism of teratogenic action as corticoids. Our preliminary evidence indicates that the teratogenic mechanism of glucocorticoids involves an H-2 regulated cytosolic receptor, inhibition of arachidonic acid and prostaglandin release, of shelf elevation, and of medial edge epithelial breakdown. This grant will investigate the role of phenytoin in each of the steps of this hypothesized teratogenic mechanism.